A Study to Evaluate the Efficacy and Safety of Adjunctive KarXT for the Treatment of Mania, With or Without Mixed Features, in Participants With Bipolar-I Disorder Taking Lithium, Valproate, or Lamotrigine

Официальное название

A Phase 3, Randomized, Double-blind, Placebo-controlled, Study to Evaluate the Efficacy and Safety of Adjunctive KarXT for the Treatment of Mania, With or Without Mixed Features, in Individuals With Bipolar-I Disorder Taking Lithium, Valproate, or Lamotrigine

Обзор

The purpose of this study is to evaluate the efficacy and safety of adjunctive KarXT for the treatment of mania in participants with Bipolar-I Disorder.

Вмешательства

• Препарат Xanomeline/Trospium Chloride
  Specified dose on specified days
• Препарат Placebo
  Specified dose on specified days

Первичные конечные точки

• Change from baseline in Young Mania Rating Scale (YMRS) at Week 5 [Срок оценки: At Week 5]

Вторичные конечные точки (11)

• Change from baseline in Clinical Global Impressions Bipolar (CGI-BP) at Week 5 [Срок оценки: At Week 5]
• Occurrence of response at Week 5 assessed as the number of participants with a ≥ 50% decrease from baseline in Young Mania Rating Scale (YMRS) score [Срок оценки: At Week 5]
• Occurrence of response at Week 5 assessed as the number of participants with a ≥ 1 change from baseline in CGI-BP [Срок оценки: At Week 5]
• Number of participants with Treatment-emergent Adverse Events (TEAEs) [Срок оценки: Up to Week 7]
• Number of participants with Serious Adverse Events (SAEs) [Срок оценки: Up to Week 7]
• Number of participants with TEAEs leading to treatment discontinuation [Срок оценки: Up to Week 5]
• Change from baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) [Срок оценки: Up to Week 7]
• Change from baseline in Barnes Akathisia Rating Scale (BARS) at Week 5 [Срок оценки: At Week 5]
• Change from baseline in Simpson Angus Scale (SAS) at Week 5 [Срок оценки: At Week 5]
• Change from baseline in Abnormal Involuntary Movement Scale (AIMS) at Week 5 [Срок оценки: At Week 5]
• Change from baseline in International Prostate Symptom Score (IPSS) at Week 5 [Срок оценки: At Week 5]

Критерии участия

Критерии включения

• Individuals have a primary diagnosis of Bipolar-I disorder established by a comprehensive psychiatric evaluation based on the DSM-5-TR criteria and confirmed by the Mini International Neuropsychiatric Interview (MINI) version 7.0.2.
• Individual is experiencing an acute exacerbation or relapse of manic episode, with or without mixed features (≤ 3 weeks).
• The individual requires hospitalization for the acute exacerbation or relapse of mania.
• Body mass index ≥ 18 and ≤ 40 kg/m2.
• Currently experiencing an acute episode of mania or mania with mixed features with a therapeutic dose of lithium, valproate, or lamotrigine. The dose of the mood stabilizer must have remained stable for at least two weeks prior to screening. Additionally, participants on valproate must have been receiving treatment with valproate for a minimum of seven months.
• YMRS Total Score of ≥ 18 at Screening and at Baseline, and < 20% reduction in YMRS from screening to baseline.

Критерии исключения

• Any primary DSM-5-TR disorder other than BP-I within 12 months before screening (confirmed using MINI version 7.0.2 at screening) including BP-I depression (for previous 3 months only), BP-I with rapid cycling, first manic episode, BP-II, primary psychotic disorder, borderline personality disorder, and major depressive disorder, with the exception of mild anxiety disorders.
• Individual has a DSM-5-TR diagnosis of moderate to severe substance use disorder (except tobacco use disorder) within the 12 months before screening (confirmed using MINI version 7.0.2 at screening), or current use as determined by urine toxicology screen or alcohol test.
• Risk for suicidal behavior at screening as determined by the investigator's clinical assessment and the C-SSRS with an answer "Yes" to item 4 or 5 within 6 months before screening or between screening and baseline, or "Yes" to any of the 5 items (C-SSRS behavior) with an event occurring within the 12 months before screening, or between screening and baseline.
• History of irritable bowel syndrome (with or without constipation) or any serious constipation requiring treatment within the last 6 months.
• History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma.
• Participants with HIV, cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections based on either medical history or the LFT results.
• Elevations in hepatic transaminases at screening ≥ 2 × ULN for ALT or AST and/or bilirubin > 1.5× ULN, unless in the context of Gilbert's syndrome.
• All grades of hepatic impairment (mild \[Child-Pugh Class A\], moderate \[Child-Pugh Class B\], and severe \[Child-Pugh Class C\]).
• Other protocol-defined Inclusion/Exclusion criteria apply.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 20 центров

• Pillar Clinical Research - Bentonville — Bentonville
• Pillar Clinical Research- Little Rock — Little Rock
• Clinical Innovations, Inc. dba CITrials — Bellflower
• Inland Psychiatric Medical Group. — Chino
• Proscience Research Group — Culver City
• Omega Clinical Trials - La Habra — La Habra
• Catalina Research Institute, LLC — Montclair
• NRC Research Institute — Orange
• … и ещё 12 центров

Япония · 13 центров

• Okehazama Hospital — Toyoake
• Local Institution - 0205 — Ichikawa
• Local Institution - 0172 — Iizuka
• Local Institution - 0141 — Kitakyushu-shi
• Goryokai Medical Corporation - Goryokai Hospital — Sapporo
• Local Institution - 0107 — Yokohama
• Rainbow and Sea Hospital — Karatsu
• Juntendo University Hospital — Bunkyo-ku
• … и ещё 5 центров

Украина · 12 центров

Список центров уточняется — проверьте первичный протокол.

Китай · 11 центров

• Local Institution - 0185 — Пекин
• Local Institution - 0190 — Пекин
• Local Institution - 0191 — Гуанчжоу
• Local Institution - 0193 — Baoding
• Local Institution - 0187 — Shijiazhuang
• Local Institution - 0196 — Нанкин
• Local Institution - 0186 — Сиань
• Local Institution - 0192 — Чэнду
• … и ещё 3 центра

Румыния · 11 центров

Список центров уточняется — проверьте первичный протокол.

Аргентина · 6 центров

• Local Institution - 0011 — ABB
• Local Institution - 0010 — Córdoba
• Local Institution - 0012 — Córdoba
• Local Institution - 0008 — Córdoba
• Local Institution - 0009 — Mendoza
• Local Institution - 0114 — Santiago del Estero

Болгария · 5 центров

• Local Institution - 0184 — Kazanlak
• State Psychiatric Hospital Sv. Ivan Rilski Novi Iskar — Novi Iskar
• "University Multiprofile Hospital for Active Treatment - Dr. Georgi Stranski" EAD — Pleven
• Local Institution - 0181 — Sliven
• Local Institution - 0086 — Targovishte

Франция · 5 центров

• Local Institution - 0126 — Nice
• Local Institution - 0085 — Clermont-Ferrand
• Local Institution - 0087 — Marseille
• Local Institution - 0129 — Montpellier
• Local Institution - 0089 — Paris

Израиль · 5 центров

• Local Institution - 0052 — Hod HaSharon
• Sheba Medical Center — Ramat Gan
• Local Institution - 0053 — Ashkelon
• Be'er Sheva Mental Health Center — Beersheba
• Local Institution - 0083 — Jerusalem

Италия · 5 центров

• Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico — Milan
• Local Institution - 0005 — Pisa
• Azienda Ospedaliero Universitaria Senese — Siena
• Local Institution - 0004 — Ancona
• Local Institution - 0002 — Genova

Индия · 4 центра

• Local Institution - 0121 — Mangalore
• Local Institution - 0123 — Madurai
• Local Institution - 0118 — Kolkata
• Local Institution - 0116 — Kolkata

Польша · 4 центра

• Instytut Psychiatrii i Neurologii — Warsaw
• Uniwersyteckie Centrum Kliniczne — Gdansk
• Local Institution - 0103 — Rybnik
• … и ещё 1 центр

Дания · 3 центра

• Local Institution - 0088 — Hillerød
• Local Institution - 0054 — Aalborg
• Local Institution - 0091 — Glostrup Municipality

Идентификаторы

NCT: NCT07140913 · CN012-0046 · 2025-521845-26 · U1111-1321-1513

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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